Smith unravels secrets of nature’s catalysts

When Janet Smith was an undergraduate at Indiana University of Pennsylvania, she attended a seminar on cytochrome c structure, sequence and phylogeny. “I thought proteins were just wonderful,” she said. “I was fascinated by the structural details and how the conservation of cytochrome c sequences mapped to the 3D structure, but didn’t have an opportunity to study protein structure until I was a postdoc. It’s the discovery … Sometimes you look at a new protein structure and immediately say, ‘Oh, wow. Now I get it.’ It’s a great thrill.”

Janet Smith

Some four decades later, Smith was still busy piecing together protein structural puzzles when she learned she had won the American Society for Biochemistry and Molecular Biology’s 2022 Mildred Cohn Award in Biological Chemistry.

“It was a complete surprise, a very pleasant surprise,” she said, describing the award as “a recognition of my service activities to help advance the structural biology field.”

In her lab at the University of Michigan, Smith and her team use X-ray crystallography, notably the multi-wavelength anomalous diffraction method and its single-wavelength counterpart, known as MAD and SAD, to solve structures of proteins such as biosynthetic enzymes for natural products and primary metabolites. As a new assistant professor, her first research projects required specialized synchrotron beamlines, leading to her effort to develop high-performance beamlines for macromolecular crystallography.

“One of the most satisfying aspects of my career has been to watch my field change from ‘protein crystallography’ to ‘structural biology,’” Smith said. “I have been fortunate to see protein structure become prospective in biochemistry and molecular biology, no longer retrospective.”

Smith lectures internationally on structural biology and synchrotron radiation and mentors young women in science and young crystallographers, even if they don’t work in her lab. Mentoring is her hardest job, she said. “Science changes … and it can be difficult to choose a path in research. I advise new students to choose any experimental area where they enjoy the work, and to consider what fields they think will be strong in 20 years. And then look at the intersection. And be fearless about changing course as science — and they — change.”